Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

Luc Y. Dirix, Istvan Takacs, Guy Jerusalem, Petros Nikolinakos, Hendrik Tobias Arkenau, Andres Forero-Torres, Ralph Boccia, Marc E Lippman, Robert Somer, Martin Smakal, Leisha A. Emens, Borys Hrinczenko, William Edenfield, Jayne Gurtler, Anja von Heydebreck, Hans Juergen Grote, Kevin Chin, Erika P. Hamilton

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Abstract

Purpose: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Oct 23 2017

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Keywords

  • Avelumab
  • Metastatic breast cancer
  • PD-L1
  • Second-line
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dirix, L. Y., Takacs, I., Jerusalem, G., Nikolinakos, P., Arkenau, H. T., Forero-Torres, A., Boccia, R., Lippman, M. E., Somer, R., Smakal, M., Emens, L. A., Hrinczenko, B., Edenfield, W., Gurtler, J., von Heydebreck, A., Grote, H. J., Chin, K., & Hamilton, E. P. (Accepted/In press). Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Research and Treatment, 1-16. https://doi.org/10.1007/s10549-017-4537-5